AIM: To compare the effectiveness of hybrid therapy with other recommended regimens using metaanalysis.METHODS: Bibliographical searches for randomized trials comparing hybrid and other therapies were performed in Pub...AIM: To compare the effectiveness of hybrid therapy with other recommended regimens using metaanalysis.METHODS: Bibliographical searches for randomized trials comparing hybrid and other therapies were performed in Pubmed, the Cochrane Library and relevant congresses up to February 2015 using the following keywords(all fields and/or me SH):("Helicobacter pylori " or "H. pylori") and("hybrid therapy" or "sequential-concomitant therapy"). metaanalyses were performed with Cochrane Review manager 5.1. The random effect model proposed by Der Simonian and Laird and the mantel-Haenszel method were used to estimate the pooled relative risk and 95%CI of the efficacy outcomes between hybrid therapy and other eradication therapies. RESULTS: Eight studies(2516 subjects) met entry criteria. The antimicrobial resistance in the study groups ranged from 6.9% to 23.5%. The mean cure rates of hybrid therapy by intention-to-treat(ITT) and perprotocol analyses were 88.5%(n = 1207; range: 80.0% to 97.4%) and 93.3%(n = 1109; range: 85.7% to99.1%), respectively. meta-analysis showed there was no significant difference in ITT eradication rate between hybrid and sequential therapy(relative risk: 1.01; 95%CI: 0.92-1.11). Subgroup analysis revealed hybrid therapy was more effective than sequential therapy in the non-Italian populations(95%CI: 1.01-1.18) and was only less effective in one, Italian population(95%CI: 0.83-0.98). There was no significant difference in eradication rate between hybrid therapy and concomitant therapy(95%CI: 0.93-1.02). No head-tohead comparisons of hybrid therapy and standard triple therapy or bismuth quadruple therapy were found. However, a multicenter, randomized trial showed that reverse hybrid therapy was superior to standard triple therapy(95.5% vs 88.6% ITT; P = 0.011).CONCLUSION: Hybrid therapy appears to be an effective, safe, and well-tolerated treatment for H. pylori infection in the era of increasing antibiotic resistance.展开更多
AIM: To compare hybrid therapy(HT) with traditional sequential therapy(ST) and concomitant therapy(CT) for Helicobacter pylori(H. pylori) eradication.METHODS: We performed an electronic search of Pub Med, Embase, and ...AIM: To compare hybrid therapy(HT) with traditional sequential therapy(ST) and concomitant therapy(CT) for Helicobacter pylori(H. pylori) eradication.METHODS: We performed an electronic search of Pub Med, Embase, and the CENTRAL database. Randomized controlled trials(RCTs) of HT were included in the meta-analysis. The primary outcome was the eradication rate of H. pylori. The secondary outcomes included the compliance rate and adverse event rate. Effect estimates were pooled using the random-effects model.RESULTS: Twelve studies were included. Pooled results showed no significant differences in eradication rate between HT and ST in per-protocol(PP) analysis(RR = 1.03, 95%CI: 0.94-1.12, P = 0.59) or in intention-totreat(ITT) analysis(RR = 1.00, 95%CI: 0.89-1.12, P = 0.94). HT and ST showed similarly high compliance rate(96% vs 98%, P = 0.55) and acceptable adverse event rate(30.3% vs 28.2%, P = 0.63). No significant results were seen in the eradication rate between HT and CT in PP analysis(RR = 1.01, 95%CI: 0.96-1.05, P = 0.76) or in ITT analysis(RR = 0.99, 95%CI: 0.95-1.03, P = 0.47). HT displayed a slightly higher compliance rate than CT(95.8% vs 93.2%, P < 0.05). The adverse event rates of HT and CT were similar(39.5% vs 44.2%, P = 0.24).CONCLUSION: Compared with ST or CT, HT yields a similar eradication rate, high compliance rate, and acceptable safety profiles.展开更多
AIM: To evaluate the efficacy of sequential vs hybrid therapy in patients with Helicobacter pylori(H. pylori) infection.METHODS: From March 2013 to May 2014,one hundred and seventy-five H. pylori infected patients who...AIM: To evaluate the efficacy of sequential vs hybrid therapy in patients with Helicobacter pylori(H. pylori) infection.METHODS: From March 2013 to May 2014,one hundred and seventy-five H. pylori infected patients who had not been treated for H. pylori before wererandomized to receive either sequential therapy(rabeprazole 20 mg and amoxicillin 1 g twice daily for 5 d,followed by rabeprazole 20 mg,clarithromycin 500 mg and metronidazole 500 mg twice daily for 5 d) or hybrid therapy(rabeprazole 20 mg and amoxicillin 1 g for 7 d,followed by rabeprazole 20 mg,amoxicillin 1 g,clarithromycin 500 mg and metronidazole 500 mg twice daily for 7 d). H. pylori status was confirmed by positive results of both rapid urease test and histology examination or a positive result of culture. Eradication efficacy was assessed by follow-up endoscopy with rapid urease test and histological examination 8 wk after the end of anti-H. pylori therapy,or 13C-urea breath test at least 4 wk after completion of treatment. The primary outcome was H. pylori eradication by intension-to-treat(ITT) and per-protocol(PP) analyses.RESULTS: One hundred and sixty-seven patients(83 patients in the sequential group and 84 patients in the hybrid group) completed the study. The compliance rates were 97.6% and 97.7% for the two groups,respectively. The eradication rate was 78.2% for the sequential group and 92% for the hybrid group by ITT analysis(P = 0.01). The eradication rate was 81.9% for the sequential group and 96.4% for the hybrid group by PP analysis(P = 0.01). Univariate analysis for the clinical and bacterial factors did not identify any risk factors associated with treatment failure. Severe adverse events were observed in 2.3% of patients in the sequential group and 2.4% of those in the hybrid group.CONCLUSION: Due to a grade A(> 95%) success rate for H. pylori eradication by PP analysis,similar compliance and adverse events,hybrid therapy seems to be an appropriate eradication regimen in Taiwan.展开更多
AIM To evaluate the impact of cytochrome P450 2C19(CYP2C19) and interleukin-1β(IL-1β) polymorphisms on the efficacy of Helicobacter pylori(H. pylori) eradication by using rabeprazole-based hybrid therapy.METHODS A t...AIM To evaluate the impact of cytochrome P450 2C19(CYP2C19) and interleukin-1β(IL-1β) polymorphisms on the efficacy of Helicobacter pylori(H. pylori) eradication by using rabeprazole-based hybrid therapy.METHODS A total of 88 H. pylori-infected patients were recruited to receive 14-d of hybrid therapy from March 2013 to May 2014. Three patients were excluded from analysis because of incomplete compliance. Either a follow-up endoscopy or 13 C-urea test was performed to determine the results of H. pylori eradication therapy. The genotypes of CYP2C19 and IL-1β were analyzed to investigate the impact on treatment effect. RESULTS The total eradication rate of H. pylori was 92.94%(79/85). According to the CYP2C19 genotypes, the rates of H. pylori eradication were 89.19% in extensive metabolizers(EM) and 95.83% in non-EM. The H.pylori eradication rates regarding the IL-1β genotypes were 92.59% in the normal acid secretion group and 93.10% in the low acid secretion group. After multivariable logistic regression analysis, both the genotypes of CYP2C19 and IL-1β had no significant influences on the eradication rates of H. pylori.CONCLUSION The CYP2C19 and IL-1β polymorphisms are not significantly independent factors of H.pylori eradication using rabeprazole-based hybrid therapy.展开更多
Hypoxia is a feature of solid tumors and it hinders the therapeutic efficacy of oxygen-dependent cancer treatment.Herein,we have developed all-organic oxygen-independent hybrid nanobullets ZPA@HA-ACVA-AZ for the“prec...Hypoxia is a feature of solid tumors and it hinders the therapeutic efficacy of oxygen-dependent cancer treatment.Herein,we have developed all-organic oxygen-independent hybrid nanobullets ZPA@HA-ACVA-AZ for the“precise strike”of hypoxic tumors through the dual-targeting effects from surface-modified hyaluronic acid(HA)and hypoxia-dependent factor carbonic anhydrase IX(CA IX)-inhibitor acetazolamide(AZ).The core of nanobullets is the special zinc(II)phthalocyanine aggregates(ZPA)which could heat the tumor tissues upon 808-nm laser irradiation for photothermal therapy(PTT),along with the alkyl chain-functionalized thermally decomposable radical initiator ACVA-HDA on the side chain of HA for providing oxygen-independent alkyl radicals for ablating hypoxic cancer cells by thermodynamic therapy(TDT).The results provide important evidence that the combination of reverse hypoxia hallmarks CA IX as targets for inhibition by AZ and synergistic PTT/TDT possess incomparable therapeutic advantages over traditional(reactive oxygen species(ROS)-mediated)cancer treatment for suppressing the growth of both hypoxic tumors and their metastasis.展开更多
Physical therapy students can experience elevated levels of stress due to the pressure to be successful, changes in the environment, personal concerns, the lack of spare time, increased work, or financial burdens. The...Physical therapy students can experience elevated levels of stress due to the pressure to be successful, changes in the environment, personal concerns, the lack of spare time, increased work, or financial burdens. The purpose of this study was to examine the perceived stress and coping strategies of Doctor of Physical Therapy (DPT) students enrolled in a hybrid-learning curriculum during the COVID-19 pademic. A total of 73 students enrolled in the DPT hybrid-learning curriculum responded to a survey which consisted of socio-demographics, the 10-item Perceived Stress Scale (PSS), and the 28-item Brief COPE. A general question regarding stress relating to COVID-19 was presented as a sliding percentage. Data analysis included a Spearman correlation, a Kruskal-Wallis test, and a linear regression to evaluate coping mechanisms against PSS scores. The mean (± SD) score on the PSS was 22.65 (± 10.21) and the Brief COPE was 59.18 (± 10.61). A non-significant negative correlation was found between the PSS and Brief COPE (r = -0.024). A third of the variation in the perceived stress score could be accounted for by students utilizing coping mechanisms regardless of other factors (R<sup>2</sup> = 0.35). No significant differences were found when comparing PSS and Brief Cope to age, hours worked per week and term. Perceived stress was higher in females compared to males, but the results were not significant. Stress related to COVID-19 mean percentage reported by DPT students was 49.03%. During a global pandemic, DPT students enrolled in a hybrid-learning curriculum reported elevated levels of stress but reported higher adaptive versus maladaptive coping strategies. It can be beneficial that universities evaluate the stress and coping methods of students to potentially avoid the negative impacts of stress.展开更多
With the rising prevalence of antimicrobial resistance,the treatment success of standard triple therapy has recently declined to unacceptable levels (i.e.,80% or less) in most countries.Therefore,several treatment reg...With the rising prevalence of antimicrobial resistance,the treatment success of standard triple therapy has recently declined to unacceptable levels (i.e.,80% or less) in most countries.Therefore,several treatment regimens have emerged to cure Helicobacter pylori (H.pylori) infection.Novel first-line anti-H.pylori therapies in 2011 include sequential therapy,concomitant quadruple therapy,hybrid (dual-concomitant) therapy and bismuth-containing quadruple therapy.After the failure of standard triple therapy,a bismuth-containing quadruple therapy comprising a proton pump inhibitor (PPI),bismuth,tetracycline and metronidazole can be employed as rescue treatment.Recently,triple therapy combining a PPI,levofloxacin and amoxicillin has been proposed as an alternative to the standard rescue therapy.This salvage regimen can achieve a higher eradication rate than bismuth-containing quadruple therapy in some regions and has less adverse effects.The best second-line therapy for patients who fail to eradicate H.pylori with first-line therapies containing clarithromycin,amoxicillin and metronidazole is unclear.However,a levofloxacin-based triple therapy is an accepted rescue treatment.Most guidelines suggest that patients requiring third-line therapy should be referred to a medical center and treated according to the antibiotic susceptibility test.Nonetheless,an empirical therapy (such as levofloxacin-based or furazolidone-based therapies) can be employed to terminate H.pylori infection if antimicrobial sensitivity data are unavailable.展开更多
The rising prevalence of antibiotic resistance has created a need to reassess the established Helicobacter pylori(H.pylori)eradication protocols,and to develop new ones.Various bacterial and host factors are evaluated...The rising prevalence of antibiotic resistance has created a need to reassess the established Helicobacter pylori(H.pylori)eradication protocols,and to develop new ones.Various bacterial and host factors are evaluated,and their contribution to eradication failure is estimated.For a long time being considered the cornerstone eradication scheme,the standard triple therapy has been replaced with novel,more efficient regimens,namely sequential and concomitant,along with the emergence of a new design of bismuth quadruple therapy.A rescue levofloxacin based regimen has overcome the fear of therapy failure due to higher prevalence of dual resistant(clarithromycin and metronidazole)H.pylori.Culture-free and efficient susceptibility test are reestablishing the concept of tailored therapy,making eradication success close to originally desirable rates.Alleviating therapy side effects and improving patient compliance are as important as choosing appropriate eradication schemes,so various probiotic compound supplements are taken into consideration.Finally,we summarize the emerging efforts and obstacles in creating efficientH.pylori vaccine.展开更多
Objective:To investigate the therapeutic effects of hybrid renal replacement therapy (HRRT) in patients with severe snake bite. Methods: 15 patients treated with HRRT from July in 2005 to August in 2009 were involved ...Objective:To investigate the therapeutic effects of hybrid renal replacement therapy (HRRT) in patients with severe snake bite. Methods: 15 patients treated with HRRT from July in 2005 to August in 2009 were involved in the study, all patients were established ascular access by central venous catheter, polysulfone membrane connected absorption hemoperfusion cartridge, the blood flow rate was 200 ml/min, the dialysate flow rate was 300 ml/min, heparin or low molecular heparin was used as anticoagulant, treatment time was 6 to 12 hours. Observe the biochemical indicators and APACHE II score before and after HRRT and clinical outcomes of the patients. Results: The level of serum creatinine, glutamic-oxalacetic transaminease, glutamic-pyruvic transaminease, creatine kinase isozyme MB, and creatine kinase were significantly lower than the level before HRRT(P<0.05); the level of cholinesterase was significantly higher than the level before HRRT (P<0.01); the APACHE II score before HRRT was 14.1±3.8, but decreased significantly to 7.9±1.4, 6.2±1.1 and 4.2±0.8 at the first, second and seventh day after HRRT, respectively (P<0.01). There are 3 patients died at the first, third, and fourth HRRT, respectively, the rest 12 patients were cured or improved when discharged, the survival rate was 80%, and the mortality was 20%. Conclusion: HRRT may be an effective treatment method for severe snake bite patients, which can reduce the mortality rate and increase the survival rate.展开更多
Live bacteria-based drug delivery systems have been raised as promising tools for enhancing drug delivery into tumors due to their active tumor targeting and easy surface modifiability.In this work,a“Trojan nanobacte...Live bacteria-based drug delivery systems have been raised as promising tools for enhancing drug delivery into tumors due to their active tumor targeting and easy surface modifiability.In this work,a“Trojan nanobacteria hybrid”,E.coli@highly integrated nanocapsules(HINCs)hybrid(HINE-Hybrid),was successfully constructed with HINCs of prodrug based on covalent selfassembly and the facultative anaerobic bacterium E.coli MG 1655 for combined chemotherapy,photothermal therapy(PTT),and chemodynamic therapy(CDT).HINCs were constructed by covalent cross-linking of pillar[5]arene derivatives and cisplatin prodrug linker,which can be endocytosed and lysed to release therapeutic agents.Under the near-infrared(NIR)light(at 808 nm)irradiation,the system temperature can be significantly increased by HINCs,which further leads to the highly efficient generation of reactive oxygen species(ROS).In addition,HINE-Hybrid shows significant antitumor effects in in vitro and in vivo studies and also promotes immune cell infiltration and antitumor cytokine expression in the tumor microenvironment(TME).HINEHybrid exerts its anticancer properties efficiently due to selective enrichment and multiplication of E.coli at tumor sites,which is important for the construction of bacterial-assisted antitumor platforms.展开更多
Antimicrobial photodynamic therapy(aPDT)has been considered a noninvasive and effective modality against the bacterial infection of peri‑implantitis,especially the aPDT triggered by near-infrared(NIR)light due to the ...Antimicrobial photodynamic therapy(aPDT)has been considered a noninvasive and effective modality against the bacterial infection of peri‑implantitis,especially the aPDT triggered by near-infrared(NIR)light due to the large penetration depth in tissue.However,the complexity of hypoxia microenvironments and the distance of aPDT sterilization still pose challenges before realizing the aPDT clinical application.Due to the long lifespan and transmission distance of therapeutic gas molecules,we design a multi-functional gas generator that combines aPDT as well as O_(2) and CO gas release function,which can solve the problem of hypoxia(O_(2))in PDT and the problem of inflammation regulation(CO)in the distal part of peri‑implant inflammation under near-infrared(NIR)irradiation.In the composite nanoplatform that spin-coated on the surface of titanium implants,up-conversion nanoparticles(UCNPs)were involved in converting the NIR to visible,which further excites the partially oxidized stannic sulfide(SnS_(2)),realizing the therapeutic gas release.Indocyanine green(ICG)was further integrated to enhance the aPDT performance(Ti-U@SnS_(2)/I).Therefore,reactive oxygen species(ROS),CO,and O_(2) can be controllably administered via a composite nano-platform mediated by a single NIR light(808 nm).This implant surface modification strategy could achieve great self-enhancement antibacterial effectiveness and regulate the lingering questions,such as relieving the anoxic microenvironment and reaching deep infection sites,providing a viable antibiotic-free technique to combat peri‑implantitis.展开更多
基金Supported by Research Foundation of the Kaohsiung Veterans General HospitalNo.VGHKS103-58
文摘AIM: To compare the effectiveness of hybrid therapy with other recommended regimens using metaanalysis.METHODS: Bibliographical searches for randomized trials comparing hybrid and other therapies were performed in Pubmed, the Cochrane Library and relevant congresses up to February 2015 using the following keywords(all fields and/or me SH):("Helicobacter pylori " or "H. pylori") and("hybrid therapy" or "sequential-concomitant therapy"). metaanalyses were performed with Cochrane Review manager 5.1. The random effect model proposed by Der Simonian and Laird and the mantel-Haenszel method were used to estimate the pooled relative risk and 95%CI of the efficacy outcomes between hybrid therapy and other eradication therapies. RESULTS: Eight studies(2516 subjects) met entry criteria. The antimicrobial resistance in the study groups ranged from 6.9% to 23.5%. The mean cure rates of hybrid therapy by intention-to-treat(ITT) and perprotocol analyses were 88.5%(n = 1207; range: 80.0% to 97.4%) and 93.3%(n = 1109; range: 85.7% to99.1%), respectively. meta-analysis showed there was no significant difference in ITT eradication rate between hybrid and sequential therapy(relative risk: 1.01; 95%CI: 0.92-1.11). Subgroup analysis revealed hybrid therapy was more effective than sequential therapy in the non-Italian populations(95%CI: 1.01-1.18) and was only less effective in one, Italian population(95%CI: 0.83-0.98). There was no significant difference in eradication rate between hybrid therapy and concomitant therapy(95%CI: 0.93-1.02). No head-tohead comparisons of hybrid therapy and standard triple therapy or bismuth quadruple therapy were found. However, a multicenter, randomized trial showed that reverse hybrid therapy was superior to standard triple therapy(95.5% vs 88.6% ITT; P = 0.011).CONCLUSION: Hybrid therapy appears to be an effective, safe, and well-tolerated treatment for H. pylori infection in the era of increasing antibiotic resistance.
基金Supported by National Science and Technology Pillar Program of 12th Five-Year Plan in China,No.2012BAI06B02Clinical Key Projects of Peking University Third Hospital,No.Y76493-03Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal Diseases in Beijing,No.BZ0371
文摘AIM: To compare hybrid therapy(HT) with traditional sequential therapy(ST) and concomitant therapy(CT) for Helicobacter pylori(H. pylori) eradication.METHODS: We performed an electronic search of Pub Med, Embase, and the CENTRAL database. Randomized controlled trials(RCTs) of HT were included in the meta-analysis. The primary outcome was the eradication rate of H. pylori. The secondary outcomes included the compliance rate and adverse event rate. Effect estimates were pooled using the random-effects model.RESULTS: Twelve studies were included. Pooled results showed no significant differences in eradication rate between HT and ST in per-protocol(PP) analysis(RR = 1.03, 95%CI: 0.94-1.12, P = 0.59) or in intention-totreat(ITT) analysis(RR = 1.00, 95%CI: 0.89-1.12, P = 0.94). HT and ST showed similarly high compliance rate(96% vs 98%, P = 0.55) and acceptable adverse event rate(30.3% vs 28.2%, P = 0.63). No significant results were seen in the eradication rate between HT and CT in PP analysis(RR = 1.01, 95%CI: 0.96-1.05, P = 0.76) or in ITT analysis(RR = 0.99, 95%CI: 0.95-1.03, P = 0.47). HT displayed a slightly higher compliance rate than CT(95.8% vs 93.2%, P < 0.05). The adverse event rates of HT and CT were similar(39.5% vs 44.2%, P = 0.24).CONCLUSION: Compared with ST or CT, HT yields a similar eradication rate, high compliance rate, and acceptable safety profiles.
文摘AIM: To evaluate the efficacy of sequential vs hybrid therapy in patients with Helicobacter pylori(H. pylori) infection.METHODS: From March 2013 to May 2014,one hundred and seventy-five H. pylori infected patients who had not been treated for H. pylori before wererandomized to receive either sequential therapy(rabeprazole 20 mg and amoxicillin 1 g twice daily for 5 d,followed by rabeprazole 20 mg,clarithromycin 500 mg and metronidazole 500 mg twice daily for 5 d) or hybrid therapy(rabeprazole 20 mg and amoxicillin 1 g for 7 d,followed by rabeprazole 20 mg,amoxicillin 1 g,clarithromycin 500 mg and metronidazole 500 mg twice daily for 7 d). H. pylori status was confirmed by positive results of both rapid urease test and histology examination or a positive result of culture. Eradication efficacy was assessed by follow-up endoscopy with rapid urease test and histological examination 8 wk after the end of anti-H. pylori therapy,or 13C-urea breath test at least 4 wk after completion of treatment. The primary outcome was H. pylori eradication by intension-to-treat(ITT) and per-protocol(PP) analyses.RESULTS: One hundred and sixty-seven patients(83 patients in the sequential group and 84 patients in the hybrid group) completed the study. The compliance rates were 97.6% and 97.7% for the two groups,respectively. The eradication rate was 78.2% for the sequential group and 92% for the hybrid group by ITT analysis(P = 0.01). The eradication rate was 81.9% for the sequential group and 96.4% for the hybrid group by PP analysis(P = 0.01). Univariate analysis for the clinical and bacterial factors did not identify any risk factors associated with treatment failure. Severe adverse events were observed in 2.3% of patients in the sequential group and 2.4% of those in the hybrid group.CONCLUSION: Due to a grade A(> 95%) success rate for H. pylori eradication by PP analysis,similar compliance and adverse events,hybrid therapy seems to be an appropriate eradication regimen in Taiwan.
文摘AIM To evaluate the impact of cytochrome P450 2C19(CYP2C19) and interleukin-1β(IL-1β) polymorphisms on the efficacy of Helicobacter pylori(H. pylori) eradication by using rabeprazole-based hybrid therapy.METHODS A total of 88 H. pylori-infected patients were recruited to receive 14-d of hybrid therapy from March 2013 to May 2014. Three patients were excluded from analysis because of incomplete compliance. Either a follow-up endoscopy or 13 C-urea test was performed to determine the results of H. pylori eradication therapy. The genotypes of CYP2C19 and IL-1β were analyzed to investigate the impact on treatment effect. RESULTS The total eradication rate of H. pylori was 92.94%(79/85). According to the CYP2C19 genotypes, the rates of H. pylori eradication were 89.19% in extensive metabolizers(EM) and 95.83% in non-EM. The H.pylori eradication rates regarding the IL-1β genotypes were 92.59% in the normal acid secretion group and 93.10% in the low acid secretion group. After multivariable logistic regression analysis, both the genotypes of CYP2C19 and IL-1β had no significant influences on the eradication rates of H. pylori.CONCLUSION The CYP2C19 and IL-1β polymorphisms are not significantly independent factors of H.pylori eradication using rabeprazole-based hybrid therapy.
基金the National Natural Science Foundation of China(51903203,51703178,81770728)the China Postdoctoral Science Foundation(2019M653661,2019M663742)+3 种基金the Natural Science Foundation of Shaanxi Province(2020JQ-046)Natural Science Foundation of Zhejiang Province(LWY20H180002)the Natural Science Foundation of Guangxi Zhuang Autonomous Region(2017GXNSFBA198028).Y.H.,M.G.,Y.S.Z.,G.H.and X.Z.were not supported by any of these fundsinstead,support by MIT,Harvard,Stanford University and the Brigham Research Institute are acknowledged.
文摘Hypoxia is a feature of solid tumors and it hinders the therapeutic efficacy of oxygen-dependent cancer treatment.Herein,we have developed all-organic oxygen-independent hybrid nanobullets ZPA@HA-ACVA-AZ for the“precise strike”of hypoxic tumors through the dual-targeting effects from surface-modified hyaluronic acid(HA)and hypoxia-dependent factor carbonic anhydrase IX(CA IX)-inhibitor acetazolamide(AZ).The core of nanobullets is the special zinc(II)phthalocyanine aggregates(ZPA)which could heat the tumor tissues upon 808-nm laser irradiation for photothermal therapy(PTT),along with the alkyl chain-functionalized thermally decomposable radical initiator ACVA-HDA on the side chain of HA for providing oxygen-independent alkyl radicals for ablating hypoxic cancer cells by thermodynamic therapy(TDT).The results provide important evidence that the combination of reverse hypoxia hallmarks CA IX as targets for inhibition by AZ and synergistic PTT/TDT possess incomparable therapeutic advantages over traditional(reactive oxygen species(ROS)-mediated)cancer treatment for suppressing the growth of both hypoxic tumors and their metastasis.
文摘Physical therapy students can experience elevated levels of stress due to the pressure to be successful, changes in the environment, personal concerns, the lack of spare time, increased work, or financial burdens. The purpose of this study was to examine the perceived stress and coping strategies of Doctor of Physical Therapy (DPT) students enrolled in a hybrid-learning curriculum during the COVID-19 pademic. A total of 73 students enrolled in the DPT hybrid-learning curriculum responded to a survey which consisted of socio-demographics, the 10-item Perceived Stress Scale (PSS), and the 28-item Brief COPE. A general question regarding stress relating to COVID-19 was presented as a sliding percentage. Data analysis included a Spearman correlation, a Kruskal-Wallis test, and a linear regression to evaluate coping mechanisms against PSS scores. The mean (± SD) score on the PSS was 22.65 (± 10.21) and the Brief COPE was 59.18 (± 10.61). A non-significant negative correlation was found between the PSS and Brief COPE (r = -0.024). A third of the variation in the perceived stress score could be accounted for by students utilizing coping mechanisms regardless of other factors (R<sup>2</sup> = 0.35). No significant differences were found when comparing PSS and Brief Cope to age, hours worked per week and term. Perceived stress was higher in females compared to males, but the results were not significant. Stress related to COVID-19 mean percentage reported by DPT students was 49.03%. During a global pandemic, DPT students enrolled in a hybrid-learning curriculum reported elevated levels of stress but reported higher adaptive versus maladaptive coping strategies. It can be beneficial that universities evaluate the stress and coping methods of students to potentially avoid the negative impacts of stress.
文摘With the rising prevalence of antimicrobial resistance,the treatment success of standard triple therapy has recently declined to unacceptable levels (i.e.,80% or less) in most countries.Therefore,several treatment regimens have emerged to cure Helicobacter pylori (H.pylori) infection.Novel first-line anti-H.pylori therapies in 2011 include sequential therapy,concomitant quadruple therapy,hybrid (dual-concomitant) therapy and bismuth-containing quadruple therapy.After the failure of standard triple therapy,a bismuth-containing quadruple therapy comprising a proton pump inhibitor (PPI),bismuth,tetracycline and metronidazole can be employed as rescue treatment.Recently,triple therapy combining a PPI,levofloxacin and amoxicillin has been proposed as an alternative to the standard rescue therapy.This salvage regimen can achieve a higher eradication rate than bismuth-containing quadruple therapy in some regions and has less adverse effects.The best second-line therapy for patients who fail to eradicate H.pylori with first-line therapies containing clarithromycin,amoxicillin and metronidazole is unclear.However,a levofloxacin-based triple therapy is an accepted rescue treatment.Most guidelines suggest that patients requiring third-line therapy should be referred to a medical center and treated according to the antibiotic susceptibility test.Nonetheless,an empirical therapy (such as levofloxacin-based or furazolidone-based therapies) can be employed to terminate H.pylori infection if antimicrobial sensitivity data are unavailable.
文摘The rising prevalence of antibiotic resistance has created a need to reassess the established Helicobacter pylori(H.pylori)eradication protocols,and to develop new ones.Various bacterial and host factors are evaluated,and their contribution to eradication failure is estimated.For a long time being considered the cornerstone eradication scheme,the standard triple therapy has been replaced with novel,more efficient regimens,namely sequential and concomitant,along with the emergence of a new design of bismuth quadruple therapy.A rescue levofloxacin based regimen has overcome the fear of therapy failure due to higher prevalence of dual resistant(clarithromycin and metronidazole)H.pylori.Culture-free and efficient susceptibility test are reestablishing the concept of tailored therapy,making eradication success close to originally desirable rates.Alleviating therapy side effects and improving patient compliance are as important as choosing appropriate eradication schemes,so various probiotic compound supplements are taken into consideration.Finally,we summarize the emerging efforts and obstacles in creating efficientH.pylori vaccine.
文摘Objective:To investigate the therapeutic effects of hybrid renal replacement therapy (HRRT) in patients with severe snake bite. Methods: 15 patients treated with HRRT from July in 2005 to August in 2009 were involved in the study, all patients were established ascular access by central venous catheter, polysulfone membrane connected absorption hemoperfusion cartridge, the blood flow rate was 200 ml/min, the dialysate flow rate was 300 ml/min, heparin or low molecular heparin was used as anticoagulant, treatment time was 6 to 12 hours. Observe the biochemical indicators and APACHE II score before and after HRRT and clinical outcomes of the patients. Results: The level of serum creatinine, glutamic-oxalacetic transaminease, glutamic-pyruvic transaminease, creatine kinase isozyme MB, and creatine kinase were significantly lower than the level before HRRT(P<0.05); the level of cholinesterase was significantly higher than the level before HRRT (P<0.01); the APACHE II score before HRRT was 14.1±3.8, but decreased significantly to 7.9±1.4, 6.2±1.1 and 4.2±0.8 at the first, second and seventh day after HRRT, respectively (P<0.01). There are 3 patients died at the first, third, and fourth HRRT, respectively, the rest 12 patients were cured or improved when discharged, the survival rate was 80%, and the mortality was 20%. Conclusion: HRRT may be an effective treatment method for severe snake bite patients, which can reduce the mortality rate and increase the survival rate.
基金This work was supported by the National Key Research and Development Program of China(Nos.2020YFA0908500 and 2018YFA0901600)the National Natural Science Foundation of China(Nos.22275046,22161142015,22075065,22001054,and 22201058)+1 种基金the Hangzhou Leading Innovation and Entrepreneurship Team Project(No.TD2022001)the startup fund from Hangzhou Normal University(No.2019QDL026).
文摘Live bacteria-based drug delivery systems have been raised as promising tools for enhancing drug delivery into tumors due to their active tumor targeting and easy surface modifiability.In this work,a“Trojan nanobacteria hybrid”,E.coli@highly integrated nanocapsules(HINCs)hybrid(HINE-Hybrid),was successfully constructed with HINCs of prodrug based on covalent selfassembly and the facultative anaerobic bacterium E.coli MG 1655 for combined chemotherapy,photothermal therapy(PTT),and chemodynamic therapy(CDT).HINCs were constructed by covalent cross-linking of pillar[5]arene derivatives and cisplatin prodrug linker,which can be endocytosed and lysed to release therapeutic agents.Under the near-infrared(NIR)light(at 808 nm)irradiation,the system temperature can be significantly increased by HINCs,which further leads to the highly efficient generation of reactive oxygen species(ROS).In addition,HINE-Hybrid shows significant antitumor effects in in vitro and in vivo studies and also promotes immune cell infiltration and antitumor cytokine expression in the tumor microenvironment(TME).HINEHybrid exerts its anticancer properties efficiently due to selective enrichment and multiplication of E.coli at tumor sites,which is important for the construction of bacterial-assisted antitumor platforms.
基金the National Natural Science Foundation of China(Nos.82170998,82201102,62205122)the Postdoctoral Science Foundation Project of China(No.2022M721316)+4 种基金the General program of the Natural Science Foundation of Jilin Province(Nos.YDZJ202201ZYTS017,20220203145SF,20210203087SF,YDZJ202201ZYTS274,YDZJ202201ZYTS080)Hygiene and Health Appropriate Technology Promotion Project of Jilin Province(No.2020S014)the Science and Technology Project of Jilin Province Financial Department(Nos.jcsz202189321,jcsz2021893-15,Zkjc D105181350043103358)Science and Technology Project of Jilin Province Education Department(No.JJKH20221098KJ)the Health Department Research Projects of Jilin Province(No.2022JC076)for financial support.
文摘Antimicrobial photodynamic therapy(aPDT)has been considered a noninvasive and effective modality against the bacterial infection of peri‑implantitis,especially the aPDT triggered by near-infrared(NIR)light due to the large penetration depth in tissue.However,the complexity of hypoxia microenvironments and the distance of aPDT sterilization still pose challenges before realizing the aPDT clinical application.Due to the long lifespan and transmission distance of therapeutic gas molecules,we design a multi-functional gas generator that combines aPDT as well as O_(2) and CO gas release function,which can solve the problem of hypoxia(O_(2))in PDT and the problem of inflammation regulation(CO)in the distal part of peri‑implant inflammation under near-infrared(NIR)irradiation.In the composite nanoplatform that spin-coated on the surface of titanium implants,up-conversion nanoparticles(UCNPs)were involved in converting the NIR to visible,which further excites the partially oxidized stannic sulfide(SnS_(2)),realizing the therapeutic gas release.Indocyanine green(ICG)was further integrated to enhance the aPDT performance(Ti-U@SnS_(2)/I).Therefore,reactive oxygen species(ROS),CO,and O_(2) can be controllably administered via a composite nano-platform mediated by a single NIR light(808 nm).This implant surface modification strategy could achieve great self-enhancement antibacterial effectiveness and regulate the lingering questions,such as relieving the anoxic microenvironment and reaching deep infection sites,providing a viable antibiotic-free technique to combat peri‑implantitis.